An Overview of National Regulatory Requirements for Biological Products in Peru
Patricia Socualaya Sotomayor, MD
Efficacy and Security AreaDirectorate of Sanitary Authorizations
General Directorate of Medicines, Supplies and Drugs (DIGEMID) Ministry of Health (MINSA), Peru
1
Outline
• Description biological products in Peru
• Legal and technical development
• Biological product distribution
• Biological product safety
• Clinical trials with biological products
• Conclusions
2
General
• Estimated population to 2014: 30 814 175 millionsof people
• Life expectancy to 2014 : 74.4 years
• GDP per capita to 2012: 17 852.69 “New Soles”per person
• Health coverage to 2012: 61.9%
• Biological Products represent 4% (514/11 625) ofall the pharmaceuticals and related products withsanitary registration in force.
3
Source: http://www.inei.gob.pe/
Biological Products manufactured
• Botropic polyvalent serum
• Antilachesico monovalentserum
• Antiloxoscelico monovalentserum
• Biolactol probioticacidophilus
• Vaccine Gel NB probiotic
• Enoxaparin
• Heparin sodium
Nowadays, 514 biological products authorized (with sanitary registration), of which 8 are locally manufactured.
4Source: Data of SIS-DIGEMID
Legal and technical development of biological products in Peru
Political Constitution
Article 118°, subsection 8
Legal Development
Law 26842, in 1997
General Health Law
Law 29459, in 2009
Law of Pharmaceuticals, Medical Devices and
Health Products
Technical Development
D.S. 010-1997
Registry Regulations, Health Surveillance and
Control of Pharmaceutical and
related Products
Includes regulations for biological products
D.S. 016-2011 and amendments
Regulation for Registration, Control and
Health Surveillance of Pharmaceutical Products,
Medical Devices and Health Products
Chapter V: biological products
Source: http://www.digemid.minsa.gob.pe/Main.asp?Seccion=7275
Regulatory change based on the Law of Pharmaceuticals, Medical Devices and Health
Products
6
D.S. 010-1997 D.S. 016-2011
- No differences between the requirements for registering chemical products and biological products
- Evaluation time: 7 days
- To Establish specific requirements for biological products
- Evaluation time: vaccines and immunological products, up to 180 days. Other biological products, the period is 12 months
Source: http://www.digemid.minsa.gob.pe/UpLoad/UpLoaded/PDF/DECRETOSUPREMON010-97-SA.pdfhttp://www.digemid.minsa.gob.pe/UpLoad/UpLoaded/PDF/DS016-2011-MINSA.pdf
D.S. 016-2011. In forceAbout of definitions of biological product
• In Peru, Biological and Biotechnological products areconsidered under the same concept: BIOLOGICAL PRODUCT
• Follows the definition of World Health Organization
7
Source: http://www.digemid.minsa.gob.pe/UpLoad/UpLoaded/PDF/DS016-2011-MINSA.pdf
D.S. 016-2011. In forceChapter V: biological products
• According to the principles of quality, efficacy and safety
• Has 12 articles
• To establish requirements for registration and re-registration
• To designate the term “Similar biological product” (article107°)
• Two pathways of register a biological product: completedossier or similarity way
Source: http://www.digemid.minsa.gob.pe/UpLoad/UpLoaded/PDF/DS016-2011-MINSA.pdf
8
D.S. 016-2011- Chapter V: biological products
Article 102°: Sanitary registration of biological products
Article 103°: In biological products
Article 104°: Requirements for registration and re-registration of biologicalproducts
Article 105°: Application contents - affidavit of registration or re-registration of biological products
Article 106°: Requirements for granting a certificate of batch release
Article 107°: Similar biological product
9
Source: http://www.digemid.minsa.gob.pe/UpLoad/UpLoaded/PDF/DS016-2011-MINSA.pdf
D.S. 016-2011- Chapter V: biological products
Article 108°: Time limits for sanitary registration of biological products
Article 109°: Labeling of mediate and immediate packaging of biologicalproducts
Article 110°: Information contained in the data sheet and insert biologicalproducts
Article 111°: Condition of sale of biological products
Article 112°: In the periodic reports of safety of biological products
Article 113°: Coding of sanitary registration of biological products
10Source: http://www.digemid.minsa.gob.pe/UpLoad/UpLoaded/PDF/DS016-2011-MINSA.pdf
Assessment process
• Peru follows and/or considers internationally acceptedstandards like those of the WHO, FDA, and EMA guidelines.
• Article 107°: Similar Biological Product … “Specific aspects ofthe quality requirements, preclinical and clinical studies ofbiological products who choose the way of similarity will beidentified in individual directives, taking into account theprogress of science and the recommendations of the WHO.”
11
Source: http://www.digemid.minsa.gob.pe/UpLoad/UpLoaded/PDF/DS016-2011-MINSA.pdf
• Has been working on the proposal of the TechnicalDocuments for:
- Similar biological products
- Biotechnological products
(full dossier)
• In the next years:
- Technical document for vaccines
- Technical document for plasma derived
This guidelines established two pathways for the approval of BPs
12
Technical Document for Similar biological products. Draft
• Recommendations for the Evaluation of Similar Biotherapeutics Productsof PARF network/WHO; as well as some specific guidelines issued by ICH,FDA, EMA and Health Canada.
• Definitions: similar biological product (SBP), reference biological product(RBP) and comparability exercise.
• SBP and RBP:- Full characterization and comparison in terms of quality are the basis forpossible data reduction in pre-clinical and clinical development.- Case by case analysis approach
• Transitional provisions
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Biological products authorized
• Has been authorized as biological products since 1998
• N total = 514 biological products with sanitary registration
• 77% (398) with sanitary registration in force
• 23% (116) in re-registration process
14
Source: Data of SIS-DIGEMID
77%
23%
In force Re- Registration process
17
9
9
9
8
8
7
6
5
5
4
3
3
1
1
8
0 2 4 6 8 10 12 14 16 18
Vacunas
Factor de Coagulación
Heparinas
Hormonas
Eritropoyetinas/Epoetinas
Insullinas
Anticuerpos Monoclonales
Inmunoglobulinas
Interferones
Enzimas
Factor Estimulante de Colonias
Sustitutos de plasma
Toxina Botulínica
Proteinas de fusion
Interleukinas
Otros
%
Biological products authorized by kind of biological products
15Source: Data of SIS-DIGEMID
N total = 514 biological products with sanitary registration
Biological products authorized from High Sanitary Surveillance Countries (HSSC)
According to with article 9°of D.S. 016 -2011
16
0
10
20
30
40
50
60
70
80
90
n
Total HSSC
N total = 514 biological products with sanitary registration
Distribution of biological product authorized
Overall, in Peru we can identify two channels of drugdistribution:
- Public Health Sector: MINSA, Regional Governments andEsSalud
- Private Health Sector
17
18
Source: Data of Access to Drugs Team of the Directorate of Access and Use of Drugs
0
5000
10000
15000
20000
25000
30000
35000
n
Consumption of biological products in EsSalud: 2012 and 2013
Consumption 2012
Consumption 2013
19Source: Data of Access to Drugs Team of the Directorate of Access and Use of Drugs
0
20000
40000
60000
80000
100000
120000
140000
160000
180000
n
Consumption of biological products in MINSA and Regional Governments: 2012 and 2013
Consumption 2012
Consumption 2013
Biological Product Safety
• n = 265 biological products withsanitary registration
• Spontaneous reporting
• 31% (82/265) of biological productsreported any adverse reactions
• 19% (49/265) of biological productsreported serious adverse reactions
20Source: Data of Pharmacovigilance Team of the Directorate of Access and Use of Drugs
Number of biological products
Vaccines 12
Monoclonal antibody 7
Enzimas 5
Hormones 5
Heparins 4
Insulins 3
Interferons 3
Erythropoietin / epoetin 2
Coagulation factors 2
Immunoglobulins 2
Colony Stimulating Factor 1
Plasma substitute 1
Others 2
TOTAL 49
Source: Data of General Office of Research and Technology Transfer - National Institute of Health
21
2012 2013
Total applications for clinical trials(chemical and biological products)
130 92
Authorized clinical trials withbiologicals
37 29
0
20
40
60
80
100
120
140
n
Clinical trials authorized with biological products: 2012 and 2013
22Source: Data of General Office of Research and Technology Transfer - National Institute of Health
0
10
20
30
40
50
60
70
Phase I Phase II Phase III Phase IV
%
Clinical Trials authorized with biological products by phases of the study: 2012 and 2013
2012
2013
23Source: Data of General Office of Research and Technology Transfer - National Institute of Health
0 5 10 15 20 25 30 35 40
Reumatology
Oncology
Neumology
Others
%
Clinical Trials authorized with biological products by medical specialty
2013
2012
Conclusions
• In Peru, approval of biological products is given in accordancewith the requirements of DIGEMID, based on “Law ofPharmaceuticals, Medical Devices and Health Products”
• Nowadays, 98% of biological products with sanitaryregistration are imported.
• Biological and Biotechnological products are considered underthe same concept: BIOLOGICAL PRODUCT
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Conclusions
• The trend in Peru is toward the adoption of acceptedinternational standards, like those presented by the WHO.
• DIGEMID is committed to ensuring the quality, efficacy andsafety of biological products.
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Acknowledgements
• General Office of Research and Technology Transfer - NationalInstitute of Health.
• Pharmacovigilance Team of the Directorate of Access and Useof Drugs.
• Access to Drugs Team of the Directorate of Access and Use ofDrugs.
• Efficacy and Security Area of Directorate of SanitaryAuthorizations.
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Thank you27